Samuel Cousin

• PhD in chemical physics
• CNRS position at Aix-Marseille University

Nuclear magnetic resonance is a ubiquitous spectroscopic tool to explore molecules with atomic resolution. Nuclear magnetic relaxation is intimately connected to molecular motions. Many methods and models have been developed to measure and interpret the characteristic rates of nuclear magnetic relaxation in proteins. These approaches shed light on...

Nuclear magnetic resonance (NMR) studies have benefited tremendously from the steady increase in the strength of magnetic fields. Spectacular improvements in both sensitivity and resolution have enabled the investigation of molecular systems of rising complexity. At very high fields, this progress may be jeopardized by line broadening, which is due...

Motions of proteins are essential for the performance of their functions. Aliphatic protein side chains and their motions play critical roles in protein interactions: for recognition and binding of partner molecules at the surface or serving as an entropy reservoir within the hydrophobic core. Here, we present a new NMR method based on high-resolut...

Purpose Diffusion MRI is of interest for clinical research and diagnosis. Whereas high‐ resolution DWI/DTI is hard to achieve by single‐shot methods, interleaved acquisitions can deliver these if motion and/or folding artefacts are overcome. Thanks to its ability to provide zoomed, folding‐free images, spatially encoded MRI can fulfill these requir...

A wide variety of nuclear magnetic resonance experiments rely on the prediction and analysis of relaxation processes. Recently, innovative approaches have been introduced where the sample travels through a broad range of magnetic fields in the course of the experiment, such as dissolution dynamic nuclear polarization or high-resolution relaxometry....

Calcium orthophosphates, such as hydroxyapatite (HAP), have been shown to follow non-classical nucleation and crystallization mechanisms involving intermediate species, including solute prenucleation species (PNS) that precede solid transient phases. Characterizing these transient soluble and solid phases in situ remains a challenge due to their sh...

Benchtop NMR is becoming an increasingly important tool, sometimes providing a simple and low-cost alternative to high-field NMR. The Achilles heel of NMR and even more critically of benchtop NMR is its limited sensitivity. However, when combined with hyperpolarization techniques, the sensitivity boost can provide excellent sensitivity that can eve...

Benchtop NMR is becoming an increasingly important tool, sometimes providing a simple and low-cost alternative to high-field NMR. The Achille’s heel of NMR and even more critically of benchtop NMR is its limited sensitivity. However, when combined with hyperpolarization techniques, the sensitivity boost can provide excellent sensitivity that can ev...

Benchtop NMR is becoming an increasingly important tool, sometimes providing a simple and low-cost alternative to high-field NMR. The Achille’s heel of NMR and even more critically of benchtop NMR is its limited sensitivity. However, when combined with hyperpolarization techniques, the sensitivity boost can provide excellent sensitivity that can ev...

Calcium ion complexation in aqueous solutions is of paramount importance in biology as it is related to cell signaling, muscle contraction, or biomineralization. However, Ca²⁺-complexes are dynamic soluble entities challenging to describe at the molecular level. Nuclear magnetic resonance appears as a method of choice to probe Ca²⁺-complexes. Howev...

Dynamic nuclear polarization (DNP) is capable of boosting signals in nuclear magnetic resonance by orders of magnitude by creating out-of-equilibrium nuclear spin polarization. The diffusion of nuclear spin polarization in the vicinity of paramagnetic dopants is a crucial step for DNP and remains yet not well understood. In this paper, we show that...

Solid-state DNP NMR can enhance the ability to detect minor amounts of solid phases within heterogenous materials. Here we demonstrate that NMR contrast based on the transport of DNP-enhanced polarization can be exploited in the challenging case of early detection of a small amount of a minor polymorphic phase within a major polymorph, and we show...

NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of 1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sen...

NMR based analysis of metabolite mixture provides crucial information on biological systems but mostly rely on 1D 1H experiments for maximizing sensitivity. However, strong peak overlap of 1H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution Dynamic Nuclear Polarization (d-DNP) improves NMR sensit...

Dynamic nuclear polarization (DNP) is capable of boosting signals in nuclear magnetic resonance by orders of magnitude by creating out-of-equilibrium nuclear spin polarization. The diffusion of nuclear spin polarization in the vicinity of paramagnetic dopants is a crucial step for DNP and remains yet not well understood. In this Letter, we show tha...

Zero- to ultralow-field nuclear magnetic resonance is a modality of magnetic resonance experiment which does not require strong superconducting magnets. Contrary to conventional high-field nuclear magnetic resonance, it has the advantage of allowing high resolution detection of nuclear magnetism through metal as well as within heterogeneous media....

Dissolution dynamic nuclear polarization (DDNP) is a versatile tool to boost signal amplitudes in solution-state nuclear magnetic resonance (NMR) spectroscopy. For DDNP, nuclei are spin-hyperpolarized "ex situ" in a dedicated DNP device and then transferred to an NMR spectrometer for detection. Dramatic signal enhancements can be achieved, enabling...

Zero- to ultralow-field nuclear magnetic resonance is a modality of magnetic resonance experiment which does not require strong superconducting magnets. Contrary to conventional high-field nuclear magnetic resonance, it has the advantage of allowing high resolution detection of nuclear magnetism through metal as well as within heterogeneous media....

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show th...

p>Dissolution-dynamic nuclear polarization can be boosted by employing multiplecontact cross-polarization techniques to transfer polarization from 1H to 13C spins. The method is efficient and significantly reduces polarization build-up times, however, it involves high-power radiofrequency pulses in a superfluid helium environment which limit its im...

Dynamic nuclear polarization (DNP) is a widely used tool for overcoming the low intrinsic sensitivity of nuclear magnetic resonance spectroscopy and imaging. Its practical applicability is typically bounded, however, by the so-called "spin diffusion barrier," which relates to the poor efficiency of polarization transfer from highly polarized nuclei...

Purpose Spatiotemporal Encoding (SPEN) is an ultrafast imaging technique where the low-bandwidth axis is rasterized in a joint spatial/k-domain. SPEN benefits from increased robustness to field inhomogeneities, folding-free reconstruction of subsampled data, and an ability to combine multiple interleaved or signal averaged scans –yet its relatively...

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has brought highly sensitive magnetic resonance to reality and has triggered the development of a plethora of promising applications in spectroscopy and imaging. Unfortunately, some severe limitations still restrain its widespread use, amongst which the experimental complexity, th...

Metabolomics plays a pivotal role in systems biology, and NMR is a central tool with high precision and exceptional resolution of chemical information. Most NMR metabolomic studies are based on 1H 1D spectroscopy, severely limited by peak overlap. 13C NMR benefits from a larger signal dispersion but is barely used in metabolomics due to ca. 6000-fo...

Magnetic resonance imaging and spectroscopy often suffer from a low intrinsic sensitivity, which can in some cases be circumvented by the use of hyperpolarization techniques. Dissolution-dynamic nuclear polarization offers a way of hyperpolarizing 13C spins in small molecules, enhancing their sensitivity by up to 4 orders of magnitude. This is usua...

Magnetic resonance imaging and spectroscopy often suffer from a low intrinsic sensitivity, which can in some cases be circumvented by the use of hyperpolarization techniques. Dissolution-dynamic nuclear polarization offers a way of hyperpolarizing 13C spins in small molecules, enhancing their sensitivity by up to 4 orders of magnitude. This is usua...

A wide variety of nuclear magnetic resonance experiments rely on the prediction and analysis of relaxation processes. Recently, innovative approaches have been introduced where the sample travels through a broad range of magnetic fields in the course of the experiment, such as dissolution dynamic nuclear polarization or high-resolution relaxometry....

Nuclear magnetic relaxation provides invaluable quantitative site-specific information on the dynamics of complex systems. Determining dynamics on nanosecond timescales requires relaxation measurements at low magnetic fields, incompatible with high-resolution NMR. Here, we use a two-field NMR spectrometer to measure carbon-13 transverse and longitu...

div> Nuclear magnetic relaxation provides invaluable quantitative site-specific information on the dynamics of complex systems. Determining dynamics on nanosecond timescales requires relaxation measurements at low magnetic fields, incompatible with high-resolution NMR. Here, we use a two-field NMR spectrometer to measure carbon-13 transverse and l...

The use of relaxation interference in the methyl Transverse Relaxation-Optimized SpectroscopY (TROSY) experiment has opened new avenues for the study of large proteins and protein assemblies in nuclear magnetic resonance. So far, the theoretical description of the methyl-TROSY experiment has been limited to the slow-tumbling approximation, which is...

The use of relaxation interference in the methyl Transverse Relaxation-Optimized SpectroscopY (TROSY) experiment has opened new avenues for the study of large proteins and protein assemblies in nuclear magnetic resonance. So far, the theoretical description of the methyl-TROSY experiment has been limited to the slow-tumbling approximation, which is...

NMR signals intensities can be enhanced by several orders of magnitude via utilization of techniques for hyperpolarization of different molecules, and it allows one to overcome the main sensitivity challenge of modern NMR/MRI techniques. Hyperpolarized fluids can be successfully used in different applications of material science and biomedicine. Th...

Many of the functions of biomacromolecules can be rationalized by the characterization of their conformational energy landscapes: the structures of the dominant states, transitions between states and motions within states. Nuclear magnetic resonance (NMR) spectroscopy is the technique of choice to study internal motions in proteins. The determinati...

Background Nitrogen-13 has a 10-min half-life which places time constraints on the complexity of viable synthetic methods for its incorporation into PET imaging agents. In exploring ways to overcome this limitation, we have used the Ugi reaction to develop a rapid one-pot method for radiolabelling peptidic molecules using [13N]NH3 as a synthetic pr...

Total correlation spectroscopy (TOCSY) is a key experiment to assign nuclear magnetic resonance (NMR) spectra of complex molecules. Carbon-13 TOCSY experiments are essential to assign signals of protein side chains. However, the performance of carbon-13 TOCSY deteriorates at high magnetic fields since the necessarily limited radiofrequency irradiat...

We present novel means to hyperpolarize deuterium nuclei in ¹³CD2 groups at cryogenic temperatures. The method is based on cross-polarization from ¹H to ¹³C and does not require any radio-frequency fields applied to the deuterium nuclei. After rapid dissolution, a new class of long-lived spin states can be detected indirectly by ¹³C NMR in solution...

Nuclear magnetic resonance (NMR) is a ubiquitous branch of spectroscopy that can explore matter at the scale of an atom. Significant improvements in sensitivity and resolution have been driven by a steady increase of static magnetic field strengths. However, some properties of nuclei may be more favourable at low magnetic fields. For example, trans...

We present the development of multiple-field liquid-state NMR spectroscopy for the determination of the structure and dynamics of small molecules and proteins. Dynamics of proteins side-chains in the pico- to nanosecond range have been studied in the protein ubiquitin, by measuring the relaxation of carbon-13 nuclei in isoleucine-δ1 methyl groups,...